Sleep apnea is a common condition that affects 4% of middle-aged males and 2% of middle-aged females. There is recent evidence that there is a genetic influence since first degree relatives of patients with this disorder have an increased risk of having obstructive sleep apnea. The basis for this increased familial risk is undefined. We postulate that there are three specific intermediate traits, each of which reduces upper airway size, thereby increasing the risk of sleep apnea. These intermediate traits include: a) particular distribution of rat in the neck; b) craniofacial structure; and c) size of critical soft tissues in the airway (soft palate, tongue, lateral pharyngeal walls). All of these risk factors can be assessed quantitatively using advanced magnetic resonance imaging (MRI) and novel volumetric image analysis techniques that we have developed. We propose that the first step to establish the genetic basis for sleep apnea is to identify the different intermediate traits involved using the imaging technology. Hence, we propose a case- control study to identify the structural risk factors for sleep apnea. This case-control study will be complemented by studies in siblings of the patients and controls in order to identify those traits that demonstrate family aggregation not explained by shared environmental factors. We believe that these structural risk factors will interact to increase the risk of sleep apnea. The elucidation of upper airway structural risk factors will provide the basis for developing new, more effective techniques for screening patients for sleep apnea and provide the basis for performing future DNA analysis aimed at identify the genetic loci for these risk factors. This proposal is based on the hypothesis that specific intermediate traits increase the risk for sleep apnea and that these intermediate traits demonstrate family aggregation. Our specific aims are: 1) to quantify upper airway craniofacial structure, soft tissues and regional fat deposition using three dimensional magnetic resonance imaging in order to determine the intermediate traits associated with obstructive sleep apnea utilizing a case control design in normals and apneics; and 2) to determine the upper airway structural risk factors for sleep apnea that demonstrate family aggregation and are most likely to have a genetic component by comparing probands, siblings of probands, neighborhood controls and siblings of neighborhood controls. Our resources, which include an extensive clinical sleep practice, sophisticated MR imaging techniques, novel volumetric computer graphics image analysis and expertise in molecular epidemiology, craniofacial structure, the genetics of obesity will allow us to achieve our specific aims.